This application is a 371 of PCT/FR00/00083 filed Jan. 14, 2000, now WO00/49028.
The invention relates to a process for preparing chiral diphosphines that are useful as bidentate ligands in the synthesis of catalysts based on transition metals intended for asymmetric catalysis.
Asymmetric catalysis has developed considerably in recent years. It has the advantage of leading directly to the preparation of optically pure isomers by asymmetric induction without it being necessary to resolve racemic mixtures.
2,2xe2x80x2-Bis(diphenylphosphino)-1,1xe2x80x2-binaphthyl (BINAP) is an example of a diphosphorus ligand commonly used to prepare metal complexes for the asymmetric catalysis of hydrogenation, carbonylation and hydrosilylation reactions, Cxe2x80x94C bond forming reactions (such as allylic substitutions or Grignard cross-couplings) or even asymmetric isomerization reactions of allylamines.
The development of novel chiral ligands is desirable so as to improve the enantioselectivity of the reactions and, more generally, the general conditions for carrying out these reactions.
The present invention more specifically provides a process for preparing diphosphorus bidentate chiral ligands of 2,2xe2x80x2-bis(diarylphosphino)-1,1xe2x80x2-binaphthyl and 2,2xe2x80x2-bis(diarylphosphino)-1,1xe2x80x2-biphenyl type that are functionalized on the binaphthyl or biphenyl groups, respectively. These ligands, coordinated to transition metals such as ruthenium or rhodium, form complexes that are useful in the asymmetric catalysis of various reactions and more particularly of asymmetric hydrogenation reactions.
The ligands prepared according to the process of the invention are in particular the dicyano derivatives of formula I: 
in which:
A represents phenyl or naphthyl; and
Ar1 and Ar2 independently represent a saturated or aromatic carbocyclic radical.
In the context of the invention, the phenyl and naphthyl radicals are optionally substituted.
According to the invention, the term xe2x80x9ccarbocyclic radicalxe2x80x9d means an optionally substituted, preferably C3-C50 monocyclic or polycyclic radical. Preferably it is a C3-C18 radical, which is preferably mono-, bi- or tricyclic.
The carbocyclic radical may comprise a saturated portion and/or an aromatic portion.
When the carbocyclic radical comprises more than one cyclic nucleus (in the case of polycyclic carbocycles), the cyclic nuclei may be fused in pairs or attached in pairs via "sgr" bonds.
Examples of saturated carbocyclic radicals are cycloalkyl groups.
Preferably, the cycloalkyl groups are saturated cyclic hydrocarbon-based radicals that are preferably C3-C18 and better still C3-C10, and in particular cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl or norbornyl radicals.
Examples of aromatic carbocyclic radicals are (C6-C18)aryl groups and in particular phenyl, naphthyl, anthryl and phenanthryl.
The substituents on the phenyl, naphthyl and carbocyclic radicals are such that they do not interfere with the reactions involved in the process of the invention. These substituents are inert under the conditions involved in bromination (step i), esterification (step ii), nucleophilic substitution (step iii) and coupling reactions.
Preferably, the substituents are alkyl or alkoxy groups.
The term xe2x80x9calkylxe2x80x9d means a saturated, linear or branched hydrocarbon-based radical containing in particular up to 25 carbon atoms and, for example, from 1 to 12 carbon atoms and better still from 1 to 6 carbon atoms.
Examples of alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, 2-methylbutyl, 1-ethylpropyl, hexyl, isohexyl, neohexyl, 1-methylpentyl, 3-methylpentyl, 1,1-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, l-methyl-1-ethylpropyl, heptyl, 1-methylhexyl, 1-propylbutyl, 4,4-di-methylpentyl, octyl, 1-methylheptyl, 2-ethylhexyl, 5,5-dimethylhexyl, nonyl, decyl, 1-methylnonyl, 3,7-dimethyloctyl and 7,7-dimethyloctyl radicals.
In a particularly advantageous manner, the dicyano derivatives of formula I are such that:
represents naphthyl or phenyl, optionally substituted with one or more radicals chosen from (C1-C6)alkyl and (C1-C6) alkoxy; and
Ar1 and Ar2 independently represent a phenyl group optionally substituted with one or more (C1-C6)alkyl or (C1-C6)alkoxy; or a (C4-C8)cyclcoalkyl group optionally substituted with one or more (C1-C6)alkyl groups.
Examples of preferred alkyl groups are, in particular, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, isopentyl, neopentyl, 2-methylbutyl, l-ethylpropyl, hexyl, isohexyl, neohexyl, 1-methylpentyl, 3-methylpentyl, 1,1-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl and 1-methyl-1-ethylpropyl.
Advantageously, the alkyl radical contains from 1 to 4 carbon atoms.
The term xe2x80x9calkoxyxe2x80x9d denotes an xe2x80x94O-alkyl radical in which alkyl is as defined above.
Advantageously, the cycloalkyl groups are chosen from cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.
It should be understood that, according to the invention, each of the naphthyl and phenyl groups representing A may be substituted.
Among the ligands of formula I that are preferred are those for which Ar1 and Ar2 are, independently, phenyl optionally substituted with methyl or tert-butyl; or (C5-C6)cycloalkyl optionally substituted with methyl or tert-butyl.
The compounds that are most particularly preferred are those of formula I in which Ar1 and Ar2 are identical. A clearly preferred meaning of Ar1 and Ar2 is optionally substituted phenyl.
Moreover, it is preferred for A to represent naphthyl optionally substituted with one to five and preferably one to two groups chosen from (C1-C6)alkyl and (C1-C6)alkoxy. Better still, A represents unsubstituted naphthyl.
When A represents optionally substituted phenyl, it is preferred for this phenyl to be substituted in the meta position relative to the group PAr1Ar2 with (C1-C6)alkyl or (C1-C6)alkoxy and better still with methyl or methoxy, the other positions of the phenyl radical being unsubstituted.
One group of compounds that is more particularly preferred consists of the compounds of formula I with a C2 axis of symmetry, with the exclusion of any element of symmetry.
The notion of the C2 axis of symmetry is described in xe2x80x9cElements of Stereochemistryxe2x80x9d, Wiley, New York, 1969 and in xe2x80x9cAdvanced Organic Chemistryxe2x80x9d, Jerry March, Stereochemistry, Chapter 4.
Among this last group of preferred compounds especially distinguished are the compounds of formulae Ia and Ib below: 
in which Ar1 and Ar2 are as defined above and S represents a substituent which is compatible with the reactions involved, and in particular alkyl or alkoxy, which is preferably C1-C6, 
in which Ar1 and Ar2 are as defined above.
The process of the invention more specifically comprises the steps consisting in:
i) brominating a diol of formula II: 
xe2x80x83in which A is as defined above, using a suitable brominating agent so as to obtain a dibromo compound of formula III: 
xe2x80x83in which A is as defined above;
ii) esterifying the compound of formula III obtained in the preceding step by the action of a sulfonic acid or an activated form thereof, so as to obtain the corresponding disulfonate;
iii) substituting the two bromine atoms with cyano groups by reacting the disulfonate obtained in the preceding step with a suitable nucleophilic agent so as to obtain the corresponding nitrile;
iv) coupling a phosphine of formula VI:
XPAr1Ar2xe2x80x83xe2x80x83VI
xe2x80x83in which X represents a hydrogen atom or a halogen atom and Ar1 and Ar2 are as defined above, with the nitrile obtained in the preceding step, in the presence of a catalyst based on a transition metal, so as to obtain the expected compound of formula I.
In step (i), the phenyl or naphthyl nucleus, respectively, of the diol of formula II is brominated by the action of a suitable brominating agent.
When A is an unsubstituted phenyl nucleus or a nucleus bearing a substituent in the meta position relative to the OH group, such as (C1-C6)alkyl or (C1-C6)alkoxy, the corresponding diol of formula IIa: 
in which S1 and S2 are as defined for S above or independently represent a hydrogen atom or an alkyl or alkoxy group, which is preferably C1-C6, gives the corresponding bromo compound of formula IIIa: 
in which S1 and S2 are as defined above.
When A is a naphthyl nucleus, the bromination of the corresponding diol of formula IIb: 
gives compound IIIb below: 
More generally, the hydroxyl groups present on the phenyl and naphthyl nuclei orient the electrophilic reaction such that the position of the bromine atoms on these nuclei is well defined.
The bromination reaction of phenyl or naphthyl nuclei is an electrophilic reaction which is readily performed by the action of Br2 on the corresponding diol.
This reaction may be carried out in the presence of a catalyst such as a Lewis acid and in particular iron chloride. However, since the hydroxyl groups present on the phenyl and naphthyl nuclei activate these nuclei, the bromination is readily performed in the absence of any catalyst.
The diols of formula II are so reactive that it is desirable to carry out the bromination at low temperature, for example between xe2x88x9278xc2x0 and xe2x88x9230xc2x0 C. and preferably between xe2x88x9278 and xe2x88x9250xc2x0 C.
According to one preferred embodiment of the invention, the bromination takes place in an inert aprotic solvent such as a haloaromatic hydrocarbon (for example chlorobenzene or dichlorobenzene); a nitroaromatic hydrocarbon such as a nitrobenzene; an optionally halogenated aliphatic hydrocarbon such as hexane, heptane, methylene chloride, carbon tetrachloride or dichloroethane; or an alicyclic hydrocarbon.
In general, aromatic hydrocarbons with electron-poor aromatic nuclei, i.e. nuclei bearing one or more electron-withdrawing substituents, may be used.
Preferred solvents which may be mentioned are haloaliphatic hydrocarbons and in particular methylene chloride.
As a variant, it is possible to perform the process in glacial acetic acid as solvent. Under these conditions, a solution of bromine in acetic acid is generally added dropwise to a solution of the diol II in acetic acid.
Whether the process is performed in the presence or absence of acetic acid, an excess of the brominating agent relative to the diol II is used.
Preferably, the molar ratio of the brominating agent to the diol II ranges between 2 and 5 and better still between 2 and 3.
When the process is performed in solution, the concentration of the reagents may vary within a very wide range between 0.01 and 10 mol/l, for example between 0.05 and 1 mol/l.
In step (ii), the hydroxyl functions of the diol III are esterified by the action of a sulfonic acid or an activated form thereof, so as to obtain the corresponding disulfonate.
According to the invention, the nature of the sulfonic acid used is not a deciding factor per se.
Advantageously, the sulfonic acid has the formula:
Pxe2x80x94SO2xe2x80x94OH
in which P represents a hydrocarbon-based aliphatic group; an aromatic carbocyclic group; or an aliphatic group substituted with an aromatic carbocyclic group.
The expression xe2x80x9chydrocarbon-based aliphatic groupxe2x80x9dmeans in particular an alkyl group as defined above, which is optionally substituted. The nature of the substituent is such that it does not react under the conditions of the esterification reaction. A preferred example of a substituent for an alkyl group is a halogen atom such as fluorine, chlorine, bromine or iodine.
The expression xe2x80x9caromatic carbocyclic groupxe2x80x9d means mono- or polycyclic aromatic groups and in particular the mono-, bi- or tricyclic groups defined above, and for example phenyl, naphthyl, anthryl or phenanthryl.
The aromatic carbocyclic group is optionally substituted. The nature of the substituent is not critical provided that it does not react under the esterification conditions. Advantageously, the substituent is optionally halogenated alkyl, alkyl being as defined above and halogen representing chlorine, fluorine, bromine or iodine, and preferably chlorine. As an example, xe2x80x9coptionally halogenated alkylxe2x80x9d denotes perfluoroalkyl such as trifluoromethyl or pentafluoroethyl.
According to one preferred embodiment of the invention, the sulfonic acid has the formula:
Pxe2x80x94SO2xe2x80x94OH
in which P represents (C6-C10)aryl optionally substituted with one or more optionally halogenated (C1-C6)alkyl; optionally halogenated (C6-C10)alkyl; or (C6-C10)aryl (C1-C6)alkyl in which the aryl group is optionally substituted with one or more optionally halogenated (C1-C6)alkyl and the alkyl group is optionally halogenated.
Suitable examples of such sulfonic acids are paratoluenesulfonic acid, methanesulfonic acid and trifluoromethanesulfonic acid, the latter being particularly preferred.
According to one preferred embodiment of the invention, an activated derivative of the sulfonic acid is used. The term xe2x80x9cactivated derivativexe2x80x9d denotes a sulfonic acid in which the acid function xe2x80x94SO3H is activated, for example by formation of an anhydride bond or an xe2x80x94SO3Cl group.
One sulfonic acid derivative which is particularly advantageous is the symmetrical anhydride of trifluoromethanesulfonic acid, of formula (CF3xe2x80x94SO2)2O.
When the sulfonic acid has the formula Pxe2x80x94SO3H above or is an activated form of this acid, the disulfonate obtained after step ii) corresponds to formula IV: 
in which A and P are as defined above.
The conditions of the esterification reaction will be readily developed by those skilled in the art. These conditions depend in particular on the nature of the esterifying agent. When the esterifying agent is a sulfonic acid, a higher reaction temperature, of between 20 and 100xc2x0 C., may prove to be necessary. Conversely, starting with an activated form of this acid, such as an anhydride or a sulfonyl chloride, a lower temperature may be suitable. Generally, a temperature of between xe2x88x9230xc2x0 C. and 50xc2x0 C. and preferably between xe2x88x9215xc2x0 C. and 20xc2x0 C. may suffice in this case.
The esterification is preferably carried out in a solvent. Suitable solvents are, in particular, optionally halogenated aliphatic, aromatic or cyclic hydrocarbons, such as those defined above. Mention may be made of carbon tetrachloride and dichloromethane. Dichloromethane is particularly preferred. Ethers may also be used as solvent. Mention will be made, for example, of C1-C6 dialkyl ethers (diethyl ether and diisopropyl ether), cyclic ethers (tetrahydrofuran and dioxane), dimethoxyethane and diethylene glycol dimethyl ether.
When the esterifying agent is an activated form of a sulfonic acid, it is desirable to introduce a base into the reaction medium. Examples of bases are N-methylmorpholine, triethylamine, tributylamine, diisopropylethylamine, dicyclohexylamine, N-methylpiperidine, pyridine, 2,6-dimethylpyridine, 4-(1-pyrrolidinyl)pyridine, picoline, 4-(N,N-dimethylamino)-pyridine, 2,6-di-t-butyl-4-methylpyridine, quinoline, N,N-dimethylaniline and N,N-diethylaniline.
Preferred bases which will be essentially selected are pyridine and 4-dimethylaminopyridine.
The reaction may also be performed in a two-phase mixture of water and of an organic solvent such as a haloaliphatic hydrocarbon (for example carbon tetrachloride). In this case, it is preferable to use an esterifying agent in anhydride form and to perform the process in the presence of a water-soluble base such as KOH, NaOH or K2CO3, preferably KOH.
The reaction of the sulfonic acid or the activated derivative thereof with the bromo diol III is stoichiometric. Nevertheless, it is preferable to perform the process in the presence of an excess of the acid or the activated form thereof. Thus, a ratio of the acid, optionally in activated form, to the diol III of between 2 and 5 and better still between 2 and 3 is recommended.
When the reaction is performed in solution, the concentration of the reagents, which is not a critical parameter according to the invention, may range between 0.1 and 10 mol/l and advantageously between 1 and 5 mol/l.
Those skilled in the art may be inspired by the operating conditions illustrated in J. Org. Chem., vol. 58, No. 7, 1993, 1945-1948 and Tetrahedron setters, vol. 31, No. 7, 985-988, 1990 for carrying out the esterification.
The following step (iii) is a nucleophilic substitution. The two bromine atoms borne by the nuclei A are displaced with cyano groups by the action of a suitable nucleophilic agent.
So as to perform this substitution, those skilled in the art may use any of the methods known in the art.
According to one preferred embodiment of the invention, the nucleophilic agent used is copper cyanide.
The molar ratio of the copper cyanide to the disulfonate is preferably greater than 2 and may advantageously range between 2 and 4 and preferably between 2 and 3.
The reaction is preferably carried out in a solvent. Examples of solvents which may be mentioned are amides such as formamide, dimethylformamide, dimethylacetamide, 2-N-methylpyrrolidinone and hexamethylphosphorylamide. Dimethylformamide is clearly preferred. Pyridine is also a suitable solvent. The reaction temperature is advantageously maintained between 50 and 200xc2x0 C., for example between 70 and 190xc2x0 C. and better still between 80 and 180xc2x0 C.
A temperature which is more particularly suitable is between 100 and 190xc2x0 C.
The concentration of the reagents in the reaction medium generally ranges between 0.1 and 10 mol/l, for example between 2 and 7 mol/l.
The isolation of the nitrile involves decomposing the intermediate complex formed and trapping the excess cyanide.
The hydrolysis of the intermediate complex may be performed either by the action of hydrated iron chloride or by the action of aqueous ethylenediamine.
In the first case, the reaction medium is poured into an aqueous 50-80% (g/ml) iron chloride solution containing concentrated hydrochloric acid. The resulting solution is heated at 40-80xc2x0 C. until the complex has completely decomposed. The medium is then separated out by settling and extracted conventionally.
In the second case, the reaction medium is poured into an aqueous ethylenediamine solution (ethylenediamine/water: 1/5-1/1 (v/v), for example 1/3) and the mixture is then stirred vigorously. The medium is then separated by settling of the phases and extracted in a manner which is known per se.
Those skilled in the art may be Inspired by the work of L. Friedman et al. published in J.O.C. 1961, 26, 1522, fur isolating the nitrile.
Starting with the disulfonate of formula IV mentioned above, the product obtained at the end of this step is the nitrile or formula V: 
in which A and P are as defined above and the position of the cyano group on the nucleus A is the same as that of the bromine in compound IV.
In the following step (iv), a cross-coupling of a phosphine of formula VI:
XPAr1Ar2xe2x80x83xe2x80x83VI
in which X is a halogen or hydrogen atom and Ar1 and Ar2 are as defined above, is carried out with the nitrile obtained in the above step, in the presence of a catalyst based on a transition metal.
This coupling leads directly to the expected compound of formula I.
Examples of suitable catalysts are catalysts based on nickel, palladium, rhodium, ruthenium or platinum or on a mixture of these metals.
The preferred catalysts are nickel-based catalysts such as those chosen from NiCl2; NiBr2; NiCl2(dppp); NiCl2(dppb); NiCl2(dppf); NiCl2(dppe); NiCl2(PPh3)2; Ni(CO)2(PPh3)2; Ni(PPh3)4 and Ni[P(PhO)3]4 in which dppe means (diphenylphosphino)ethane, dppp means (diphenylphosphino) propane, dppb means (diphenylphosphino) butane and dppf means (diphenylphosphino)ferrocenyl.
Among these catalysts, NiCl2(dppe) is preferred.
The reaction is generally carried out at a temperature of from 50 to 200xc2x0 C. and preferably from 80 to 130xc2x0 C.
The molar ratio of compound VI to the nitrile is at least 2. It generally ranges between 2 and 4, for example between 2 and 3.
The amount of catalyst is preferably such that the molar ratio of the nitrile to the catalyst ranges between 5 and 100 and in particular between 5 and 80.
The reaction is preferably performed in a polar aprotic solvent and in particular an amide such as those mentioned above. In this case also, N,N-dimethyl-formamide is preferred. Nevertheless, other types of polar solvent may be used, such as (C1-C6)alkanols (ethanol) aromatic hydrocarbons (toluene, xylene and benzene), ethers (dioxane) and acetonitrile.
The precise reaction conditions depend on the nature of the compound of formula VI involved in the reaction.
When compound VI is HPAr1Ar2, the reaction is advantageously performed in the presence of a base.
Bases that are particularly suitable are pyridine, 4-dimethylaminopyridine, 2,6-di-tert-butylpyridine, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) and 1,4-diazabicyclo-[2.2.2]octane (DABCO or triethylenediamine). DABCO will advantageously be used as base. In this case, it is preferred for the molar ratio of the nitrile to the catalyst to be between 5 and 20, for example between 7 and 15.
When the compound of formula VI is halPAr1Ar2 in which hal is a halogen atom, preferably Cl or Br (better still Cl), it is necessary to add zinc to the reaction medium.
The amount of zinc is preferably such that the molar ratio of the zinc to the halPAr1AR2 ranges between 1 and 2 and preferably between 1.2 and 1.7.
In this case, it is desirable to cool the reaction mixture containing the solvent, the nitrile and compound VI to a temperature of between xe2x88x9210xc2x0 C. and 20xc2x0 C. throughout the addition of the zinc to the reaction medium. Then, the reaction takes place by heating to a suitable temperature of between 50xc2x0 C. and 200xc2x0 C.
When the compound of formula VI is halPAr1Ar2, it is preferred for the molar ratio of the nitrile to the catalyst to be between 40 and 80, for example between 50 and 70.
For further details regarding the implementation of these coupling reactions, those skilled in the art will refer to D. Cai et al. J.O.C. 1994, 59, 7180 and D. J. Ager et al. Chem. Comm. 1997, 2359.
When A represents phenyl which is optionally substituted, preferably with (C1-C6) alkyl or (C1-C6)alkoxy, the compound obtained after step (iv) has the formula Ic: 
in which Ar1, Ar2, S1 and S2 are as defined above for formula IIa.
When A represents naphthyl, the compound obtained after step (iv) has the formula Ib: 
in which Ar1 and Ar2 are as defined above.
The compounds of formula I are ligands capable of coordinating to transition metals such as ruthenium and rhodium. When combined with these metals, the ligands form complexes that are useful in the asymmetric catalysis of enantioselective hydrogenation reactions starting with varied substrates such as xcex2-keto esters, xcex1-keto esters and dehydroamino acids.
The present invention moreover provides a process for converting the compounds of formula I (which contain two cyano functions) into corresponding diaminomethyl compounds.
As a variant, it is possible to convert the two cyano functions of the compounds of formula I into carboxylic acid, imine, hydroxymethyl or amide functions.
The products resulting from these conversions are also ligands which may be used in asymmetric catalysis.
Thus, according to another of its aspects, the invention relates to a process comprising, in addition to steps (i) to (iv) defined above, the step consisting in reducing the nitrile function of the compound of formula I by the action of a reducing agent so as to obtain a compound of formula VII: 
in which A, Ar1 and Ar2 are as defined above.
A suitable reducing agent is lithium aluminum hydride (LiAlH4).
The invention is not intended to be limited to the use of this particular reducing agent.
The reaction is preferably carried out in a solvent or a mixture of solvents.
When the reducing agent is LiAlH4, the solvent advantageously comprises one or more aromatic hydrocarbons (such as benzene, toluene or xylene) mixed with one or more ethers.
Ethers which may be mentioned are C1-C6 alkyl ethers (diethyl ether and diisopropyl ether), cyclic ethers (dioxane and tetrahydrofuran), dimethoxyethane and diethylene glycol dimethyl ether.
Cyclic ethers such as tetrahydrofuran are preferred.
When the reducing agent is LiAlH4, a mixture of toluene and tetrahydrofuran in proportions ranging between (v/v) 70-50/30-50:toluene/tetrahydrofuran (for example 60/40:toluene/THF) will be chosen more preferably.
The reduction may be carried out at a temperature of between 20xc2x0 C. and 100xc2x0 C. and preferably between 40xc2x0 C. and 80xc2x0 C.
A large excess of the reducing agent is usually used. Thus, the molar ratio of the reducing agent to the compound of formula I generally ranges between 1 and 30, for example between 2 and 20 and in particular between 5 and 18.
The concentration of the reagents in the medium is variable; it may be maintained between 0.005 and 1 mol/l.
The compounds of formula VII obtained according to the process of the invention are novel and form another subject of the invention. Among these compounds, preference is given to those for which A represents naphthyl, which correspond to the following formula: 
in which Ar1 and Ar2 are as defined in claim 1.
A preferred group of these diamines consists of the compounds of formula VIIa in which Ar1 and Ar2 are independently chosen from phenyl optionally substituted with methyl or tert-butyl; and (C5-C6)cycloalkyl optionally substituted with methyl or tert-butyl.
Better still, preference is given to the compounds in which Ar1 and Ar2 are identical and represent optionally substituted phenyl.
As a variant, the invention provides a process comprising, in addition to steps (i) to (iv) defined above, the step consisting in treating the compound of formula I in a acidic medium or in basic medium, so as to obtain the corresponding carboxylic acid of formula VIII: 
in which A, Ar1 and Ar2 are as defined above.
The conversion of a nitrile function into a carboxylic acid function is described in organic chemistry textbooks. Thus, those skilled in the art can readily determine the appropriate reaction conditions.
One simple way of performing the process consists in using aqueous sodium hydroxide as hydrolysis agent.
The process of the invention may be carried out starting with an optically active compound II with conservation of the chirality from the start to the end of the synthesis.
With the aim of conserving the chirality, the esterification of the compound of formula III will be carried out under anhydrous conditions in the presence of suitable bases chosen from N-methylmorpholine, triethylamine, tributylamine, diisopropylethamine, dicyclohexylamine, N-methylpiperidine, pyridine, 2,6-dimethylpyridine, 4-(1-pyrrolidinyl)pyridine, picoline, 4-(N,N-dimethylamino)pyridine, 2,6-di-t-butyl-4-methylpyridine, quinoline, N,N-dimethylaniline and N,N-diethylaniline.
Thus, starting with a (S)-2,2xe2x80x2-dihydro-1,1xe2x80x2-binaphthyl, (S)-6,6xe2x80x2-dibromo-2,2xe2x80x2-dihydroxy-1,1xe2x80x2-binaphthyl and (S)-6,6xe2x80x2-dicyano-2,2xe2x80x2-bis(diarylphosphino)-1,1xe2x80x2-binaphthyl are successively obtained.
The same process applied to (R)-2,2xe2x80x2-dihydroxy-1,1xe2x80x2-binaphthyl gives (R)-6,6xe2x80x2-dicyano-2,2xe2x80x2-bis(diarylphosphino)-1,1xe2x80x2-binaphthyl.
The optically active isomers of the compounds of formula II are conventionally isolated from the corresponding racemic mixtures. An optically active resolving agent is usually Used to do this.
In the case of 1,1xe2x80x2-bis(2-naphthol), the enantiomers may be resolved by forming an inclusion complex with (R,R)-1,2-cyclohexanediamine, (R,R) or (S,S)-2,3-(+)-dimethoxy-N,N,Nxe2x80x2,Nxe2x80x2-tetramethylsuccinamide or alternatively (R,R) or (S,S)-2,3-(+)-N,N,Nxe2x80x2,Nxe2x80x2-tetramethyl-2,2xe2x80x2-dimethyl-1,3-dioxolane-trans-dicarboxamlde. These methods have been described in the literature. Another way of performing the process consists in forming an inclusion complex of 1,1xe2x80x2-bis(2-naphthol) with N-benzylcinchoninium chloride. Using acetonitrile as solvent, only the complex with one of the enantiomers precipitates, thus allowing the two enantiomers to be separated. Reference will be made in this respect to the studies by D. Cai published in Tetrahedron Letters, vol. 36, No. 44, 7991-7994, 1995.
As a variant, it is possible, in order to prepare an optically active compound of formula I, to carry out step a) starting with a racemic diol of formula II, to resolve the bromo derivative obtained of formula III and then to continue the synthesis starting with the appropriate optically active bromo compound III.
The difunctional ligands obtained according to the processes of the invention may be used in the preparation of metal complexes intended for the asymmetric catalysis of hydrogenation reactions, hydrosilylation reactions, hydroboration reactions of unsaturated compounds, epoxidation reactions of allylic alcohols, vicinal hydroxylation reactions, hydrovinylation reactions, hydroformylation reactions, cyclopropanation reactions, isomerization reactions of olefins, polymerization reactions of propylene, addition reactions of organometallic compounds to aldehydes, allylic alkylation reactions, reactions of aldol type, Diels-Alder reactions and, in general, reactions for the formation of Cxe2x80x94C bonds (such as allyl substitutions or Grignard cross-couplings).
According to one preferred embodiment of the invention, the complexes are used for the hydrogenation of Cxe2x95x90O, Cxe2x95x90C and Cxe2x95x90N bonds.
The complexes which may be used in reactions of this type are rhodium, ruthenium, palladium, platinum, iridium, cobalt, nickel or rhenium complexes, preferably rhodium, ruthenium, iridium, palladium and platinum complexes. Even more advantageously, rhodium, ruthenium or iridium complexes are used.
Specific examples of said complexes of the present invention are given below, with no limiting nature.
In the following formulae, P represents a ligand according to the invention.
A preferred group of the rhodium and iridium complexes is defined by the formula:
[MeLig2P]YIxe2x80x83xe2x80x83IX
in which:
P represents a ligand according to the invention;
YI, represents a coordinating anionic ligand;
Me represents iridium or rhodium; and
Lig represents a neutral ligand.
Among these compounds, those in which:
Lig represents an olefin containing from 2 to 12 carbon atoms;
YI represents a PF6xe2x88x92, PCl6xe2x88x92, BF4xe2x88x92, BCl4xe2x88x92, SbF6xe2x88x92, SbCl6xe2x88x92, BPh4xe2x88x92, ClO4xe2x88x92, CNxe2x88x92, CF3SO3xe2x88x92 or halogen, preferably Clxe2x88x92 or Brxe2x88x92, anion, a 1,3-diketonate, alkylcarboxylate or haloalkylcarboxylate anion with a lower alkyl (preferably C1-C6) radical, a phenylcarboxylate or phenoxide anion in which the benzene ring may be substituted with lower alkyl (preferably C1-C6) radicals and/or halogen atoms, are particularly preferred.
In formula IX, Lig2 may represent two Lig ligands as defined above or a bidentate ligand such as a linear or cyclic, polyunsaturated bidentate ligand comprising at least two unsaturations.
It is preferred according to the invention for Lig2 to represent 1,5-cyclooctadiene, norbornadiene or for Lig to represent ethylene.
The expression xe2x80x9clower alkyl radicalsxe2x80x9d generally means a linear or branched alkyl radical containing from 1 to 4 carbon atoms.
Other iridium complexes are those of formula:
[IrLigP]YIxe2x80x83xe2x80x83X
in which Lig, P and Y, are as defined for formula IX.
A preferred group of ruthenium complexes consists of the compounds of formula:
[RuYI1YI2P]xe2x80x83xe2x80x83XI
in which:
P represents a ligand according to the invention;
YI1 and YI2, which may be identical or different, represent a PF6xe2x88x92, PCl6xe2x88x92, BF4xe2x88x92, BCl4xe2x88x92, SbF6xe2x88x92, SbCl6xe2x88x92, BPh4xe2x88x92, ClO4xe2x88x92 or CF3SO3xe2x88x92 anion, a halogen atom, more particularly chlorine or bromine, or a carboxylate anion, preferably acetate or trfluoroacetate.
Other ruthenium complexes are those corresponding to formula XII below:
[RuYI3arPYI4]xe2x80x83xe2x80x83XII
in which:
P represents a ligand according to the invention;
ar represents benzene, p-methylisopropylbenzene or hexamethylbenzene;
YI3 represents a halogen atom, preferably chlorine or bromine;
YI4 represents an anion, preferably a PF6xe2x88x92, PCl6xe2x88x92, BF4xe2x88x92, BCl4xe2x88x92, SbF6xe2x88x92, SbCl6xe2x88x92, BPh4xe2x88x92, ClO4xe2x88x92 or CF3SO3xe2x88x92 anion.
It is also possible to use in the process of the invention palladium-based and platinum-based complexes.
As more specific examples of said complexes, mention may be made, inter alia, of Pd(hal)2P and Pt(hal)2P in which P represents a ligand according to the invention and hal represents halogen such as, for example, chlorine.
The complexes comprising a ligand according to the invention and the transition metal may be prepared according to the known processes described in the literature.
The complexes are generally prepared from a precatalyst whose nature varies according to the transition metal selected.
In the case of rhodium complexes, the precatalyst is, for example, one of the following compounds: [RhI(CO)2Cl]2; [RhI(COD)2Cl]2 in which COD denotes cyclooctadiene; or RhI(acac)(CO)2 in which acac denotes acetylacetonate.
In the case of ruthenium complexes, precatalysts that are particularly suitable are bis(2-methylallyl)-cycloocta-1,5-dieneruthenium and [RuCl2(benzene)]2. Mention may also be made of Ru(COD) (xcex73-(CH2)2CHCH3)2.
By way of example, starting with bis(2-methylallyl)-cycloocta-1,5-dieneruthenium, a solution or suspension is prepared containing the metallic precatalyst, a ligand and a fully degassed solvent such as acetone (the ligand concentration in the solution or suspension ranging between 0.001 and 1 mol/l), to which is added a methanolic hydrogen bromide solution. The ratio of the ruthenium to the bromine advantageously ranges between 1:1 and 1:4 and preferably between 1:2 and 1:3. The molar ratio of the ligand to the transition metal is itself about 1. It may be between 0.8 and 1.2.
When the precatalyst is [RuCl2(benzene)]2, the complex is prepared by mixing the precatalyst, the ligand and an organic solvent and optionally maintaining a temperature of between 15xc2x0 C. and 150xc2x0 C. for 1 minute to 24 hours, preferably 30xc2x0 C. to 120xc2x0 C. for 10 minutes to 5 hours.
Solvents which may be mentioned are aromatic hydrocarbons (such as benzene, toluene and xylene), amides (such as formamide, dimethylformamide, dimethylacetamide, 2-N-methylpyrrolidinone or hexamethylphosphorylamide) and alcohols (such as ethanol, methanol, n-propanol and isopropanol), and mixtures thereof.
Preferably, when the solvent is an amide, in particular dimethylformamide, the mixture of the ligand, the precatalyst and the solvent is heated to between 80xc2x0 C. and 120xc2x0 C.
As a variant, when the solvent is a mixture of an aromatic hydrocarbon (such as benzene) with an alcohol (such as ethanol), the reaction medium is heated to a temperature of between 30xc2x0 C. and 70xc2x0 C.
The catalyst is then recovered according to the conventional techniques (filtration or crystallization) and used in asymmetric reactions. Nevertheless, the reaction which needs to be catalyzed with the complex thus prepared may be carried out without intermediate isolation of the catalyst complex.
In the text hereinbelow, the case of hydrogenation is described in detail.
The unsaturated substrate, dissolved in a solvent comprising the catalyst, is placed under a pressure of hydrogen.
The hydrogenation is carried out, for example, at a pressure ranging between 1.5 bar and 100 bar, and at a temperature of between 20xc2x0 C. and 100xc2x0 C.
The exact implementation conditions depend on the nature of the substrate which needs to be hydrogenated. Nevertheless, in the general case, a pressure of from 20 bar to 80 bar and preferably from 40 bar to 60 bar, and a temperature of from 30xc2x0 C. to 70xc2x0 C., are particularly suitable.
The reaction medium may consist of the reaction medium in which the catalyst was obtained. The hydrogenation reaction then takes place in situ.
As a variant, the catalyst is isolated from the reaction medium in which it was obtained. In this case, the reaction medium for the hydrogenation reaction consists of one or more solvents, chosen in particular from C1-C5 aliphatic alcohols such as methanol or propanol and ar. amide as defined above, for example dimethylformamide, optionally mixed with benzene.
When the hydrogenation reaction takes place in situ, it is desirable to add to the reaction medium one or more solvents chosen from those mentioned above, and more particularly one or more aliphatic alcohols.
According to one preferred embodiment, fully degassed methanol and the substrate are added to the reaction medium containing the complex. The amount of methanol, or more generally of solvent, which may be added is such that the concentration of the substrate in the hydrogenation reaction medium is between 1xc3x9710xe2x88x923 and 10 mol/l and preferably between 0.01 and 1 mol/l.
The molar ratio of the substrate to the catalyst generally ranges from 1/100 to 1/100 000 and preferably from 1/20 to 1/2 000. This ratio is, for example, 1/1 000.
The rhodium complexes prepared from the ligands of the invention are more especially suitable for the asymmetric catalysis of isomerization reactions of olefins.
The ruthenium complexes prepared from the ligands of the invention are more especially suitable for the asymmetric catalysis of hydrogenation reaction of carbonyl bonds, of Cxe2x95x90C bonds and of Cxe2x95x90N bonds.
As regards the hydrogenation of double bonds, the suitable substrates are of the type such as xcex1,xcex2-unsaturated carboxylic acid and/or xcex1,xcex2-unsaturated carboxylic acid derivatives. These substrates are described in EP 95943260.0.
The xcex1,xcex2-unsaturated carboxylic acid and/or the derivative thereof corresponds more particularly to formula A: 
in which:
R1, R2, R3 and R4 represent a hydrogen atom or any hydrocarbon-based group, provided that:
if R1 is different than R2 and other than a hydrogen atom, then R3 can be any hydrocarbon-based group or functional group denoted by R,
if R1 or R2 represents a hydrogen atom and if R1 is other than R2, then R3 is other than a hydrogen atom and other than xe2x80x94COOR4,
if R1 is identical to R2 and represents any hydrocarbon-based group or functional group denoted by R, then R3 is other than xe2x80x94CHxe2x80x94(R)2, and other than xe2x80x94COOR4,
one of the groups R1, R2 and R3 possibly representing a functional group.
A specific example which may be mentioned, inter alia, is 2-methyl-2-butenoic acid.
A first group of preferred substrates is formed by substituted acrylic acids that are precursors of amino acids and/or derivatives.
The expression xe2x80x9csubstituted acrylic acidsxe2x80x9d means the set of compounds whose formula is derived from that of acrylic acid by substituting not more than two of the hydrogen atoms borne by the ethylenic carbon atoms with a hydrocarbon-based group or with a functional group.
They may be symbolized by the following chemical formula: 
in which:
R9 and Rxe2x80x29, which may be identical or different, represent a hydrogen atom, a linear or branched alkyl group containing from 1 to 12 carbon atoms, a phenyl group or an acyl group containing from 2 to 12 carbon atoms, and preferably an acetyl or benzoyl group,
R8 represents a hydrogen atom, an alkyl group containing from 1 to 12 carbon atoms, a cycloalkyl radical containing from 3 to 8 carbon atoms, an arylalkyl radical containing from 6 to 12 carbon atoms, an aryl radical containing from 6 to 12 carbon atoms or a heterocyclic radical containing from 4 to 7 carbon atoms,
R10 represents a hydrogen atom or a linear or branched alkyl group containing from 1 to 4 carbon atoms.
Mention may be made more particularly of:
methyl xcex1-acetamidocinnamate,
methyl acetamidoacrylate,
benzamidocinnamic acid,
xcex1-acetamidocinnamic acid.
A second preferred group of substrates consists of itaconic acid and derivatives thereof of formula: 
in which:
R11 and R12, which may be identical or different, represent a hydrogen atom, a linear or branched alkyl group containing from 1 to 12 carbon atoms, a cycloalkyl radical containing from 3 to 8 carbon atoms, an arylalkyl radical containing from 6 to 12 carbon atoms, an aryl radical containing 6 to 12 carbon atoms a heterocyclic radical containing from 4 to 7 carbon atoms,
R10 and Rxe2x80x210, which may be identical or different, represent a hydrogen atom or a linear or branched alkyl group containing from 1 to 4 carbon atoms.
As more specific examples, mention may be made in particular of itaconic acid and dimethyl itaconate.
A third preferred group of substrates is defined by formula A3: 
in which:
Rxe2x80x310 represents a hydrogen atom or a linear or branched alkyl group containing from 1 to 4 carbon atoms,
R13 represents a phenyl or naphthyl group optionally bearing one or more substituents.
Specific examples which may be mentioned are the substrates leading by hydrogenation to 2-(3-benzoylphenyl)proponic acid (Ketoprofen(copyright)), 2-(4-isobutylphenyl)propionic acid (Ibuprofen(copyright)) and 2-(5-methoxynaphthyl)propionic acid (Naproxen(copyright))
As regards the hydrogenation of carbonyl bonds, the appropriate substrates of ketone type correspond more preferably to formula B: 
in which:
R5 is different than R6,
R5 and R6 represent a hydrocarbon-based radical containing from 1 to 30 carbon atoms optionally comprising one or more functional groups,
R5 and R6 can form a ring optionally comprising another hetero atom,
Z is or comprises an oxygen or nitrogen hetero atom or a functional group comprising at least one of these hetero atoms.
These compounds are specifically described in FR 96/08060 and EP 97930607.3.
A first preferred group of such keto substrates has the formula B1: 
in which:
R5 is different than R6, the radicals R5 and R6 represent a hydrocarbon-based radical containing from 1 to 30 carbon atoms optionally comprising another ketone and/or acid, ester, thioacid or thioester function;
R5 and R6 can form a substituted or unsubstituted carbocyclic or heterocyclic ring containing 5 or 6 atoms.
Among these compounds, the ones that are most particularly preferred are the ketones chosen from:
methyl phenyl ketone,
isopropyl phenyl ketone,
cyclopropyl phenyl ketone,
allyl phenyl ketone,
p-methylphenyl methyl ketone,
benzyl phenyl ketone,
phenyl triphenylmethyl ketone,
o-bromoacetophenone,
xcex1-bromoacetone,
xcex1-dibromoacetone,
xcex1-chloroacetone,
xcex1-dichloroacetone,
xcex1-trichloroacetone,
xcex1-chloro-3,3-dichloroacetone
1-chloro-2-oxobutane,
1-fluoro-2-oxobutane,
1-chlorb-3-methyl-2-butanone,
xcex1-chloroacetophenone,
1-chloro-3-phenylacetone,
xcex1-methvlaminoacetone,
xcex1-dimethylaminoacetone,
1-butylamino-2-oxopropane,
1-dibutylamino-2-oxopropane,
1-methylamino-2-oxobutane,
1-dimethylamino-2-oxobutane,
1-dimethylamino-3-methyl-2-oxobutane,
1-dimethylamino-2-oxopentane,
xcex1-dimethylaminoacetophenone,
xcex1-hydroxyacetone,
1-hydroxy-3-methyl-2-butanone,
1-hydroxy-2-oxobutane,
l-hydroxy-2-oxopentane,
l-hydroxy-2-oxohexane,
1-hydroxy-2-oxo-3-methylbutane,
xcex1-hydroxyacetophenone,
1-hydroxy-3-phenylacetone,
xcex1-methoxyacetone,
xcex1-methoxyacetophenone,
xcex1-ethoxyacetone,
xcex1-butoxyacetophenone,
xcex1-chloro-p-methoxyacetophenone,
xcex1-naphthenone,
1-ethoxy-2-oxobutane,
1-butoxy-2-oxobutane,
xcex1-dimethoxyphosphorylacetone,
3-oxotetrahydrothiophene.
Substrates of aldehyde/ketone type containing a second carbonyl group in an xcex1, xcex2, xcex3 or xcex4 position relative to the first carbonyl group are also particularly suitable in the context of the invention. Examples of such diketo compounds are:
xcex1-formylacetone,
diacetyl,
3,4-dioxchexane,
4,5-dioxooctane,
1-phenyl-1,2-dioxopropane,
1-phenyl-2,3-dioxobutane,
diphenyiglyoxal,
p-methoxydiphenylglyoxal,
1,2-cyclopentanedione,
1,2-cyclohexanedione,
acetylacetone,
3,5-heptanedione,
4,6-nonanedione,
5,7-undecadione,
2,4-hexanedione,
2,4-heptanedione,
2,4-octanedione,
2,4-nonanedione,
3,5-nonanedione,
3,5-decanedione,
2,4-dodecanedione,
1-phenyl-1,3-butanedione,
1-phenyl-1,3-pentanedione,
1-phenyl-1,3-hexanedione,
1-phenyl-1,3-heptanedione,
3-methyl-2,4-pentanedione,
1,3-diphenyl-1,3-propanedione,
1,5-diphenyl-2,4-pentanedione,
1,3-bis(trifluoromethyl)-1,3-propanedione,
3-chloro-2,4-pentanedione,
1,5-dichloro-2,4-pentanedione,
1,5-dihydroxy-2,4-pentanedione,
1,5-dibenzyloxy-2,4-pentanedione,
1,5-diamino-2,4-pentanedione,
1,5-bis(methylamlno)-2,4-pentanedione,
1,5-bis(dimethylamino)-2,4-pentanedione,
methyl 3,5-dioxohexanoate,
3-carbomethoxy-2,4-pentanedione,
3-carboethoxy-2,4-pentanedione,
1,3-cyclopentanedione,
1,3-cyclohexanedione,
1,3-cycloheptanedione,
5-carboethoxy-1,3-cyclopentanedione,
2-acetyl-1-cyclopentanone,
2-acetyl-1-cyclohexanone.
As other substrates that are particularly suitable, mention may be made of keto acids or derivatives thereof and keto thioacids or derivatives thereof with a functional group (acid, ester, thioacid or thioester) in an xcex1, xcex2, xcex3 or xcex4 position relative to the carbonyl group. Examples of these are:
2-acetylbenzoic acid,
pyruvic acid,
2-oxobutanoic acid,
3-methyl-2-oxobutanoic acid,
phenylglyoxylic acid,
phenylpyruvic acid,
p-methoxyphenylpyruvic acid,
3,4-dimethoxyphenylpyruvic acid,
methyl acetoacetate,
ethyl acetoacetate,
n-propyl acetoacetate,
isopropyl acetoacetate,
n-butyl acetoacetate,
t-butyl acetoacetate,
n-pentyl acetoacetate,
n-hexyl acetoacetate,
n-heptyl acetoacetate,
n-octyl acetoacetate,
methyl 3-oxopentanoate,
methyl 3-oxohexanoate,
methyl 3-oxohexanoate,
ethyl 3-oxooctanoate,
ethyl 3-oxononanoate,
ethyl 3-oxodecanoate,
ethyl 3-oxoundecanoate,
ethyl 3-oxo-3-phenylpropanoate,
ethyl 4-phenyl-3-oxobutanoate,
methyl 5-phenyl-3-oxopentanoate,
ethyl 3-oxo-3-p-methoxyphenylpropanoate,
methyl 4-chloroacetoacetate,
ethyl 4-chloroacetoacetate,
methyl 4-fluoroacetoacetate,
ethyl 3-trifluoromethyl-3-oxopropanoate,
ethyl 4-hydroxy-3-oxobutanoate,
methyl 4-methoxyacetoacetate,
methyl 4-tert-butoxyacetoacetate,
methyl 4-benzyloxy-3-oxobutanoate,
ethyl 4-benzyloxy-3-oxobutanoate,
methyl 4-amino-3-oxobutanoate,
ethyl 3-methylamino-3-oxobutanoate,
methyl 4-dimethylamino-3-oxobutanoate,
ethyl 4-dimethylamino-3-oxobutanoate,
methyl 2-methylacetoacetate,
ethyl 2-methylacetoacetate,
ethyl 2-chloroacetoacetate,
diethyl 2-acetylsuccinate,
diethyl 2-acetylglutarate,
dimethyl acetylmalonate,
thiomethyl acetoacetate,
thioethyl acetoacetate,
thiophenyl acetoacetate,
methyl pyruvate,
ethyl 3-methyl-2-oxobutanoate,
ethyl phenylglyoxolate,
methyl phenylpyruvate,
ethyl phenylpyruvate,
3-oxobutanoic dimethylamide,
3-oxobutanoic benzylamide,
2-carboethoxycyclopentanone,
2-carboethoxycyclohexanone,
ketopentalacetone,
4-oxopentanoic acid,
4-oxohexanoic acid,
4-oxoheptanoic acid,
4-oxodecanoic acid,
4-oxododecanoic acid,
4-phenyl-4-oxybutyric acid,
4-p-methoxyphenyl-4-oxobutyric acid,
4-(3,4-dimethoxyphenyl)-4-oxobutyric acid,
4-(3,4,5-trimethoxyphenyl)-4-oxobutyric acid,
4-p-chlorophenyl-4-oxybutyric acid,
4-phenyl-4-oxobutyric acid.
It shoulid be noted that when a xcex3-keto acid or derivative needs to be asymmetrically hydrogenated, the product obtained is generally a xcex3-butyrolactone derivatIve and, in the case of a xcex4-keto acid, it is a valerolactone derivative.
Other examples of ketones which may be mentioned, inter alia, are the following monocyclic or polycyclic, saturated or unsaturated cyclic keto compounds: 
in which R represents a phenyl which is unsubstituted or substituted with alkyl or alkoxy radicals or a halogen atom; or R represents an alkyl or cycloalkyl group which is unsubstituted or substituted with alkyl or alkoxy radicals or a halogen atom, a hydroxyl, ether or amine group; or R represents a halogen atom or a hydroxyl, alkoxy or amine group.
Ketones of steroid type may also be used (for example 3-cholestanone or 5-cholesten-3-one). 
Other keto substrates which may be mentioned are the compounds of formula B2: 
in which:
R5, which is other than R6, have the meaning given above,
R7 represents:
a hydrogen atom,
a hydroxyl group,
a group OR17,
a hydrocarbon radical R17,
a group of formula 
a group of formula 
with R14, P15, R16 and R17 which represent a hydrogen atom or a hydrocarbon-based group containing from 1 to 30 carbon atoms.
Examples of compounds of formula B2 are:
xe2x86x92N-alkylketoimines, such as:
N-isobutyl-2-iminopropane
N-isobutyl-1-methoxy-2-iminopropane
xe2x86x92N-arylalkylketoimines, such as:
N-benzyl-1-imino-1-(phenyl)ethane
N-benzyl-1-imino-1-(4-methoxyphenyl)ethane
N-benzyl-1-imino-1-(2-methoxyphenyl)ethane
xe2x86x92N-arylketoimines, such as:
N-phenyl-2-iminopentane
N-(2,6-dimethylphenyl)-2-iminopentane
N-(2,4,6-trimethylphenyl)-2-iminopentane
N-phenyl-1-imino-1-phenylethane
N-phenyl-1-methoxy-2-iminopropane
N-(2,6-dimethylphenyl)-1-methoxy-2-iminopropane
N-(2-methyl-6-ethyiphenyl)-1-methoxy-2-iminopropane
xe2x86x92compounds of hydrazone type, optionally N-acylated or N-benzoylated:
1-cyclohexyl-1-(2-benzoylhydrazono)ethane,
1-phenyl-1l-(2-benzoylhydrazono)ethane,
1-p-methoxyphenyl-1-(2-benzoylhydrazono)ethane,
1-p-ethoxyphenyl-1-(2-benzoylhydrazono)ethane,
1-p-nitroiphenyl-1-(2-benzoylhydrazono)ethane,
1-p-bromophenyl-1-(2-benzoylhydrazono)ethane,
1-p-carboethoxyphenyl-1-(2-benzoylhydrazono)ethane,
1,2-diphenyl-1-(2-benzoylhydrazono)ethane,
3-methyl-2-(2-p-dimethylaminobenzoylhydrazono)butane,
1-phenyl-1-(2-p-methoxybenzoylhydrazono)ethane,
1-phenyl-1-(2-p-dimethylaminobenzoylhydrazono)ethane,
ethyl 2-(2-benzoylhydrazono)propionate,
methyl 2-(2-benzoylhydrazono)butyrate,
methyl 2-(2-benzoylhydrazono)valerate,
methyl 2-phenyl-2-(2-benzoylhydrazono)acetate.
Other starting substrates are semicarbazones and cyclic keto imines containing an endocyclic or exocyclic bond, such as: 
According to one particularly preferred embodiment of the invention, the substrate is a xcex2-keto ester (such as methyl acetoacetate or methyl 3-oxovalerate), an xcex1-keto ester (such as methyl benzoylformate or methyl pyruvate), a ketone (such as acetophenone), an olefin, an unsaturated amino acid or a derivative thereof (in particular an ester thereof).
The complexes obtained from the ligands of formula I and the derivatives thereof give, in particular, good enantioselectivity in hydrogenation reactions.
More particularly, the ruthenium complexes prepared from the ligands obtained according to the process of the invention are suitable for the asymmetric catalysis of hydrogenation reactions of the Cxe2x95x90O bonds of xcex2-keto esters.
The ruthenium complexes and ligands of formula VII are particularly suitable for the asymmetric catalysis of hydrogenation reactions of the Cxe2x95x90O bonds of ketones.
Thus, according to another of its aspects, the invention relates to the use of a compound of formula I or of formula VII or of formula VIII for the preparation of a metal complex intended for asymmetric catalysis, and more especially a ruthenium, iridium or rhodium complex.
The use of a ligand of formula VII for the preparation of a metal complex and more specifically a ruthenium complex, intended for the asymmetric catalysis of hydrogenation reactions of ketones, forms a preferred subject of the invention.